This research project is concerned with the study of autoantibodies in the sera of patients with connective tissue diseases. These autoantibodies arise spontaneously in patients with systemic lupus erythematosus, mixed connective tissue disease, Sjogren's syndrome and scleroderma. Many of these antibodies react specifically with non-histone proteins complexed to chromosomes. One of the objectives is to characterize each nuclear antigen-antibody system. Information obtained to date has shown that antibodies to different non-histone proteins are present in different disease conditions. In other words, diseases such as systemic lupus erythematosus or scleroderma have their own characteristic profiles of antibodies to nuclear non-histone proteins. Thus, characterization of the specificities of these antibodies can be used as markers in differential diagnosis. The naturally occurring autoantibodies have also been used as reagents to isolate nuclear non-histone proteins. We have characterized a centromere (kinetochore) antigen with the use of one of these reagent antibodies. Work in progress is currently concerned with the isolation and characterization of other non-histone chromosomal proteins which react with autoimmune antibodies.